Safety and efficiency of repeat salvage lymph node dissection for recurrence of prostate cancer using PSMA-radioguided surgery (RGS) after prior salvage lymph node dissection with or without initial RGS support.

BACKGROUND AND OBJECTIVE: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND). MATERIALS AND METHODS: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery. RESULTS AND LIMITATIONS: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size. CONCLUSION: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery.

[Salvage lymphadenectomy for recurrent prostate cancer]. / Salvage-Lymphadenektomie beim Prostatakarzinom.

Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging allows early detection of metastases in patients with biochemical recurrence. Salvage lymphadenectomy became a widely used method of metastasis-directed treatment. Retrospective analyses show that a low prostate-specific antigen (PSA) value and presence of no more than two affected lymph nodes within the pelvis are factors associated with a good outcome. In all, 40-80% of patients achieve a complete biochemical response with a mean time without biochemical recurrence of 8 months and a prolonged treatment-free interval. About 10% of patients with a complete biochemical response will live without recurrence after 10 years. The utilization of PSMA-radioguided surgery increases the likelihood of intraoperative detection of suspicious affected lymph nodes. Complications can mostly be avoided by prudent patient selection and surgical expertise.

Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen-targeted Salvage Surgery.

BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Prevalence of bilateral loco-regional spread in unilateral pelvic PSMA PET positive recurrent prostate cancer.

BACKGROUND: Defining the best surgical template for salvage lymph node dissection (SLND) in patients exhibiting unilateral prostate cancer (PCa) recurrence in pelvic lymph nodes (LNs) is an unmet need. We assessed the risk of missing contralateral nodal recurrence in patients with unilateral positive PSMA-PET who were treated with bilateral PSMA-radioguided (RGS) SLND. METHODS: Patients who consecutively underwent bilateral PSMA-radioguided SLND for PCa recurrence between April 2014 and January 2023 were identified. We compared PSMA PET findings with the number and the location of PCa LN metastases of the final pathological report. Univariable logistic regression models to try to predict contralateral missed disease were performed. RESULTS: Sixty patients were identified. At PSMA-RGS, the median PSA level was 0.71 ng/mL (IQR: 0.38-2.28). At PSMA-PET pre-SLND, 49 (82%) patients had unilateral exclusively pelvic lesions, 2 (3%) had unilateral positive nodes at the level of the common iliac arteries, and 9 (15%) had unilateral positive nodes in both levels. Final pathology revealed unilateral LN involvement in 43 (72%), a negative report in 3 (5%), and bilateral positive lesions in 14 (23%) patients. In the univariable logistic regression models, none of the tested factors showed influence on missing contralateral lesions. Four patients out of 35 (11%) with one positive LN at PSMA-PET had bilateral PCa recurrence. CONCLUSIONS: Patients with one-sided positive LNs on PSMA PET can be considered for a unilateral PSMA-radioguided SLND template with the caveat that about a quarter of patients ultimately have bilateral positive LNs. Larger prospective randomized trials are needed to confirm our findings.